Box 3.

The “neurodegenerative subtype” of Senile dementia

The “neurodegenerative subtype”, as understood by the present authors, was based on severe primary atrophy of [cortical] ganglion cells [nerve cells, neurons], with insignificant atheromatous vascular changes. It is possible that this subtype foreshadowed the disease he later described, regarding another presenile demented patient he encountered in 1901 (Auguste D.) and whose brain he studied in 1906. The Bielschowsky’s silver staining technique that appeared in 1903 permitted identification of remarkable “neurofibrillary changes” (sehr merkwürdige Veränderungen der Neurofibrillen), and additionally, “miliary nodules” (miliare Herdchen), mostly abundant in the superficial layers. This “new disease”1 was later designated as “Alzheimer’s disease”2,20.

Alzheimer also assumed that “…in cases of typical Senile dementia, degenerative changes of the ganglion cells might appear, independent of a vascular disease”6. This supposition was soon confirmed by Fischer’s studies on Presbyophrenic dementia (Die presbyophrene Demenz) (from Presbyophrenie, according to Wernicke)22, a clinical form of Senile dementia (senile Verblödung), according to Kraepelin2. In 1907, Fischer described plaques (drusigen Nekrosen, Sphaerotrichia cerebri multiplex)21, apparently the main focus of his study at the time. In 1910, he went on to describe neurons with “neurofibrillary changes” (“grobfaserige Fibrillenwucherung der Ganglienzellen”) in a number of senile cases22.

Thus, plaques (miliare Herdchen, drusigen Nekrosen) and neurofibrillary changes (sehr merkwürdige Veränderungen der Neurofibrillen, grobfaserige Fibrillenwucherung der Ganglienzellen), found in presenile and senile cases, became a hallmark of the neurodegenerative subtype of the disease.